Many factors are thought to cause ankle ligament injuries. The purpose of this study was to examine injury risk factors prospectively and determine if an abnormality in any one or a combination of factors identifies an individual, or an ankle, at risk for subsequent inversion ankle injury. We examined 145 college-aged athletes before the athletic season and measured generalized joint laxity, anatomic foot and ankle alignment, ankle ligament stability, and isokinetic strength. These athletes were monitored throughout the season. Fifteen athletes incurred inversion ankle injuries. Statistical analyses were performed using both within-group (uninjured versus injured groups) data and within-subject (injured versus uninjured ankles) data. No significant differences were found between the injured (N = 15) and uninjured (N = 130) groups in any of the parameters measured. However, the eversion-to-inversion strength ratio was significantly greater for the injured group compared with the uninjured group. Analysis of the within-subject data demonstrated that plantar flexion strength and the ratio of dorsiflexion to plantar flexion strength was significantly different for the injured ankle compared with the contralateral uninjured ankle. Individuals with a muscle strength imbalance as measured by an elevated eversion-to-inversion ratio exhibited a higher incidence of inversion ankle sprains. Ankles with greater plantar flexion strength and a smaller dorsiflexion-to-plantar flexion ratio also had a higher incidence of inversion ankle sprains.